Cytokinetics Announces the Initiation of Phase I Clinical Trial

Cytokinetics to Receive Milestone Payment from GlaxoSmithKline under Broad Alliance

South San Francisco, CA - August 12, 2002

Cytokinetics, Inc. today announced the initiation of a Phase I clinical trial of a small-molecule inhibitor of kinesin spindle protein (KSP). Initiation of this trial triggers an undisclosed milestone payment from GlaxoSmithKline plc to Cytokinetics under the terms of the collaboration established in June 2001 between the two companies to discover, develop and commercialize novel small-molecule therapeutics for the treatment of cancer and other diseases.

This first Phase I study is an open-label, non-randomized, dose-finding trial being conducted to investigate the safety, tolerability, pharmacokinetic, and pharmacodynamic profile of the KSP inhibitor. The study is being conducted at two clinical centers in the United States (CTRC Institute for Drug Development, affiliated with the University of Texas Health Science Center in San Antonio, Texas and the University of Wisconsin Comprehensive Cancer Center in Madison, Wisconsin) in patients with advanced cancers.

“Cytokinetics has achieved uncommonly rapid success in translating our expertise and focus on the cytoskeleton into our first anti-cancer drug candidate,” stated Dr. James Sabry, Cytokinetics’ President and Chief Executive Officer. “Initiation of human clinical trials of our first KSP inhibitor with GlaxoSmithKline represents a significant milestone under the broad strategic alliance initiated just one year ago. We are now entering the next phase of our collaboration as we embark on investigating the potential of this biology to generate a new class of therapeutics in cancer.”

“Cytotoxic anti-mitotic compounds currently serve as the foundation for a majority of existing anti-cancer regimens and, looking forward, will likely continue to occupy a prominent role in the oncology armamentarium,” stated Dr. Eric Rowinsky, Director of Clinical Research at the CTRC Institute for Drug Development. “We are excited to be beginning the clinical evaluation of this promising compound in the setting of various human cancers. A novel small-molecule anti-mitotic that offers the potential of a broader therapeutic index would have clinical impact.”

Under the terms of the collaboration, GlaxoSmithKline has committed funding of approximately $50 million over the minimum 5-year research term, including a $14 million upfront cash payment and a $14 million purchase of Cytokinetics preferred stock. In addition, GlaxoSmithKline could make milestone payments to Cytokinetics ranging from $30-50 million per target for products directed to each of over 10 mitotic kinesins that will be the subject of collaborative activities. GlaxoSmithKline is responsible for worldwide development and commercialization of products arising from the collaboration. Cytokinetics will receive royalties from the sale of any resulting products. In addition, Cytokinetics retains a product-by-product option to co-fund certain development activities, thereby increasing its royalty and affording co-promotion rights in North America. During the collaboration, targets may revert to Cytokinetics for independent research and development, with GlaxoSmithKline retaining an option to resume joint activities.

Background
KSP is required at the earliest stages of mitosis, and is the mitotic kinesin for which the biological function is best understood. Kinesins are enzymes that translate chemical energy into mechanical force along intracellular filaments in order to carry out important biological functions. The mitotic kinesins are a functional subgroup of kinesins that work in an ordered fashion to facilitate the mechanical processes required for mitosis and the division of DNA during cell division. Academic and biopharmaceutical research activities have demonstrated that these enzyme targets are amenable to small-molecule perturbation thereby disrupting mitotic spindle function, interrupting DNA and cell division and inducing apoptosis or cell death. In April 2002, at the annual meeting of the American Association for Cancer Research, Cytokinetics and GlaxoSmithKline jointly unveiled the results of intensive research efforts in the field of mitotic kinesins, which included the breadth of anti-tumor activity observed for KSP inhibitors in multiple preclinical studies of cancer. These studies spanned more than ten different models, including human colon cancers and carcinomas of the breast, ovary, lung and pancreas, measuring the activities of KSP inhibitors relative to standard controls including irinotecan, topotecan, gemcitabine, paclitaxel, vinblastine, and cyclophosphamide. Details of preclinical anti-tumor activity are complemented by observations demonstrating the absence of neuropathy in animal models. These preclinical data generate the hypotheses that KSP inhibitors may be clinically effective anti-tumor agents, and that such agents may be well tolerated by cancer patients. However, the clinical relevance of the findings needs to be determined. Cytokinetics and GlaxoSmithKline are engaging in a broad-based clinical development program to test these hypotheses.

Since the introduction of anti-mitotic drugs 20 years ago, these agents (taxanes and vinca alkaloids), which affect tubulin polymerization, have dramatically advanced cancer patient care and have served as a cornerstone of modern chemotherapy. However, use of these agents is severely constrained by dose-limiting toxicities related to the broad role that tubulin plays in important cellular processes unrelated to mitosis. In contrast, mitotic kinesins represent a family of newly identified enzymes. Each family member appears to perform a discrete and non-redundant role in mitotic spindle formation and function. Unlike tubulin, KSP and other mitotic kinesins are expressed only in proliferating cells and appear to play no role outside mitosis. Inhibitors of KSP and other mitotic kinesins may therefore represent next generation anti-mitotics, by targeting the mitotic process specifically.

About Cytokinetics
Founded in 1998 and privately held, Cytokinetics is dedicated to the discovery, development and commercialization of a novel class of therapeutics resulting from its leadership position in the emerging field of cytoskeletal pharmacology. The cytoskeleton is a complex, dynamic framework that impacts all aspects of cell function including cell division, cell motility, intracellular transport, muscle contractility and regulation of cellular organization. Cytokinetics’ R&D efforts incorporate proprietary Cytometrix™ cellular phenotyping technologies and are focused on serving pharmaceutical needs in cancer, cardiovascular and infectious diseases. For more information, please visit the company’s web site at www.cytokinetics.com.

Contacts
Cytokinetics, Inc.
Robert I. Blum
Sr. Vice President, Finance & Corporate Development
Chief Financial Officer
(650) 624-3002

Burns McClellan, Inc.
Stephanie Diaz (investors)
(415) 352-6262
Justin Jackson (media)
(212) 213-0006